2013 Lasker~DeBakey Clinical Medical Research Award

Modern cochlear implant

The 2013 Lasker~DeBakey Clinical Medical Research Award honors three scientists who developed the modern cochlear implant, a device that restores hearing to individuals with profound deafness. Through their vision, persistence, and innovation, Graeme M. Clark (Emeritus, University of Melbourne), Ingeborg Hochmair (MED-EL, Innsbruck), and Blake S. Wilson (Duke University) created an apparatus that has transformed the lives of hundreds of thousands of people. Their work has, for the first time, substantially restored a human sense with a medical intervention.

When hearing fades, so does part of the world. People miss out on conversations, their toddler's footsteps, and cars screeching around corners. Childhood deafness impairs the ability to understand spoken language and acquire speech, and these hindrances limit educational trajectories and career choices. Cochlear implants return the capacity to communicate and connect through one of the primary conduits used by the vast majority of humans.

Whispers of a solution

In normal hearing, auditory structures capture sound and translate it into information that the brain can interpret. The ear canal funnels vibrations onto the eardrum, and movements there perturb tiny bones, which propagate the fluctuations to the inner ear. Waves roll through the fluid-filled cochlea, a snail-shaped tube, and bend the thousands of delicate hair cells that lie within this organ. The displacements cause the hair cells to produce an electrical signal that stimulates the eighth cranial nerve — sometimes called the auditory nerve — and the message continues to the brain.

Within that chain of events, numerous things can go wrong. In most cases, severe hearing loss arises from damage to or absence of the sensory hair cells. Cochlear implants bypass the need for these cells by using electrical stimuli to directly excite the auditory nerve.

In the late 1950s, French doctors made a rudimentary effort to implement this idea in an individual whose hearing gear was largely gone. The system worked poorly and failed quickly, but news of the attempt reached and inspired the late otologist William House in California. He dreamed of designing a robust, easily usable prosthesis that would help deaf people hear for their lifetimes.

House developed an apparatus that delivered current through a single wire, or electrode, to a single spot on the cochlea. In 1961, two individuals received this implant. It enabled them to perceive environmental sounds, and its descendant devices helped people read lips, but speech was extremely distorted. Nevertheless, this triumph kicked off a bustle of activity among a few scientists who aimed to improve the device.

Most experts, however, did not join these pioneers, but instead cast skepticism on the enterprise. Restoration of meaningful hearing was impossible with electrical stimulation, they decried. The required neural response was far too complicated to replicate by simple and coarse signals.

Channels to hearing

Fortunately, Ingeborg Hochmair and Graeme Clark did not shy away from daunting challenges. Independently, they set out to craft an apparatus that would not only enhance awareness of the surroundings and facilitate lip reading, but would also enable deaf people to comprehend speech without visual cues. To do so, the investigators exploited a part of the auditory network that the single-electrode approach ignored.

In a person with intact cochlear hair cells, these structures beat every time sound waves hit. The perturbations cause neurons to fire in synch with the pulses, and single-electrode tactics rely on this 'time coding' system (so named because its operation depends on how often vibrations arrive). By the end of the 1960s, studies by the late Blair Simmons (Stanford University) suggested that single electrodes could reliably convey tones only up to a certain frequency. Above that point, further increases did not register as higher pitches to most people.

Simmons proposed that the time code alone would not allow faithful auditory perception; a second strategy that our brains use to decipher sound was needed in addition. The hair cells along the cochlea do not react uniformly to a given incoming pitch; their locations matter. A baby's cry awakens hair cells — and thus, the nerves they excite — at the cochlea's opening, whereas a rumbling truck disturbs those in the spiral's center. As a result, the unfurled cochlea bears similarities to a piano, with pitch proceeding in an orderly fashion from highest to lowest. Together, the 'notes' in different places communicate all tones to the brain.

Clark and Hochmair — with electrical engineer (and future husband) Erwin Hochmair — harnessed this 'place coding' phenomenon by routing particular speech sounds to different parts of the cochlea. In this way, they selectively targeted nerves that respond especially well to the frequencies received. The scientists deployed multiple electrodes, each of which resided at a different site on the cochlea's inner surface.

In addition to solving the electrical challenges, they and others in the field also tackled numerous safety and mechanical issues. For example, the devices — and the techniques for implanting them — needed to minimize infection risk, tissue damage, and hazards associated with running current through a person's body. The investigators had to find nontoxic materials that were inert to biological activities and formulate ways to thread electrode arrays deep into the cochlea and position them there.

Each of their designs includes components that, together, transform acoustical information into electrical signals that excite the auditory nerve (see Figure).

Patients were first implanted with the Hochmair and Clark inventions in December 1977 and August 1978, respectively. These multichannel prototypes dramatically upgraded speech perception. Many of today's systems mirror the basic blueprint of the original devices.

In 1985, the US Food and Drug Administration gave its inaugural approval to a multichannel cochlear implant— for treating adults who could hear before they went deaf. Three years later, an NIH consensus statement concluded that multichannel stimulation would probably produce superior speech recognition than single-channel stimulation.

Breaking sound barriers

Although the early-generation multichannel devices had propelled implants to a new performance level, many recipients could not grasp spoken words or sentences without contextual or visual hints. The next major development catapulted the technology over this hurdle.

In 1991, Blake Wilson reported a new speech-processing strategy that provides time- and place-coding information in a particularly clear way. It rapidly presents a wide range of frequency pulses that are slightly offset in time from one another, or 'interleaved'. Because no two electrodes receive a signal simultaneously, the scheme minimizes distortions and omissions. Through this and other important features, Wilson's 'continuous interleaved sampling' (CIS) system has allowed the majority of cochlear implant recipients — for the first time — to understand words and sentences with no visual cues. CIS supplies the basis for the sound-processing strategies that are now widespread and fueled an exponential growth in implant use that began in the early 1990s. Its rapid introduction, utilization, and dissemination stemmed in large part from a policy that donates to the public domain all intellectual property produced by Wilson and his colleagues from their NIH-funded cochlear-implant research.

Today, most people with cochlear implants can talk on their cell phones and follow conversations in relatively quiet environments. Experts complain that patients are doing so well, they're hitting ceilings on standard hearing tests, which lack the sensitivity to demonstrate the subtle deficits in speech comprehension that a typical recipient experiences. Additional advances are moving the field toward the ability to fine-tune hearing and thus help people fully appreciate music and understand tone languages, which are spoken by a large fraction of the planet's population.

Amplifying improvements

As of 2010, approximately 219,000 people across the globe had received cochlear implants, and more than 80% of the prostheses had been dispensed since 2000. The numbers are increasing rapidly; by the middle of 2013, more than 320,000 individuals were using cochlear implants, and almost 40,000 had one in each ear.

As the device's effectiveness has grown, so too has the number of potential candidates. Now, adults who have severe age-related hearing loss, for instance, are taking advantage of the invention.

Cochlear implants have delivered exceptionally dramatic effects to children. If a person can't hear during the first few years of life, the brain can't fully equip itself to understand and acquire speech. Early intervention is therefore crucial. Of every 1000 babies born, more than one is deaf.

Today, about 60% of implants worldwide go to children; those who live in an industrialized nation routinely receive them between age 1 and 2 years. With this intervention, many youngsters can more easily mainstream into regular schools.

Some individuals now receive implants in both ears, which is especially helpful not only to enrich hearing in general, but also for localizing speech in noisy settings. People are also combining cochlear implants with hearing aids to get the most out of both instruments; for example, electrical stimulation in the areas of the cochlea that respond to high frequencies can synergize well with hearing aids that enhance low-frequency perception.

Brilliance and relentless commitment have fueled the reverberating success of Clark, Hochmair, and Wilson. Less than a generation ago, deaf individuals had no hope of hearing again. These scientists have cracked the barriers that formerly isolated huge numbers of people from the realm of sound and have made many lives hum in new ways.

Award presentation by Jeremy Nathans

In the New Testament, we read in the Gospel of Mark that Jesus performed the miracle of restoring hearing to a deaf man. Two thousand years later, modern medical science has developed a device that can deliver the same miraculous result, although, I should note, not with the same rapidity as the procedure described in the Gospel. That device is the cochlear implant, which functions as an electronic ear, converting sounds, such as speech, into tiny electrical impulses that activate the auditory nerve.

Today we honor three pioneers — Graeme Clark, Ingeborg Hochmair, and Blake Wilson — who have devoted their professional lives to making the cochlear implant a reality. Their work, together with the work of many hundreds of engineers, audiologists, and surgeons, has brought the gift of hearing to several hundred thousand profoundly hearing-impaired individuals, a number that is climbing rapidly.

In industrialized countries, approximately one in every 1000 people is born with severe congenital hearing loss, mostly from genetic causes; in developing countries, the incidence is even higher because of intrauterine infections. Severe hearing loss can also be caused by events after birth, with the result that by early adulthood one in several hundred people has a significant hearing impairment. In later life, many individuals experience a progressive decline in hearing, especially those who have been chronically exposed to loud sounds.

The psychological effects of hearing loss can be profound. Many people have noted that, compared to vision loss, hearing loss is more often accompanied by social isolation. As Helen Keller perceptively observed, "vision connects us to things, but hearing connects us to people." For the very young, hearing impairment brings a special challenge: language acquisition begins in infancy, and for children with normal hearing this occurs via exposure to spoken language. If alternate routes are not effectively developed, a deaf child's acquisition of language will be severely impaired.

What exactly is a cochlear implant and how does it bypass damage in the middle or inner ear to restore hearing? First, we need a brief description of how the ear works. Sound consists of pressure waves propagated in the air. Complex sounds such as speech or music are made up of waves of different frequencies. The challenge for the ear is to analyze the sound intensity at each frequency. This analysis is done in a small structure called the cochlea, a spiral-shaped object that looks like a snail shell embedded in the temporal bone. Along the length of the spiral are nerve cells that function as sensors of the vibratory stimulus. Now here's a critical part of Nature's design: different frequencies are sensed by nerve cells at different locations within the cochlea, and those locations are laid out in order of frequency along the length of the cochlea. At one end of the cochlea the nerve cells sense low-pitched sounds: for example, the roar of a lion. At the other end the nerve cells sense high-pitched sounds: for example, the squeak of a mouse. At locations between these two extremes are all of the in-between frequencies, in order from lowest to highest. Importantly, the second-order nerve cells that convey sound information from the cochlea to the brain — and that generally escape damage in the hearing impaired ear — are similarly arrayed in order of frequency within the cochlea.

The cochlear implant consists of two parts. One part is worn next to the ear: it includes a microphone, a light-weight battery, a power transmitter, a signal processor, and a radio transmitter. The second part is implanted inside the skull in a delicate microsurgical procedure: it includes a power receiver, a radio frequency receiver, and a series of stimulating electrodes with each electrode located at a different position along the length of the cochlea. The signal processor on the outside separates the incoming sound into its individual frequency components and communicates that information to the implanted receiver, which then stimulates the appropriate electrodes. Because, as noted earlier, the cochlea is organized by frequency, each electrode stimulates a cluster of nerve cells that are tuned to a similar and limited set of frequencies. In practice, the recipient of a cochlear implant generally needs many weeks or months of practice until the brain learns to make sense of the new and relatively crude patterns of electrode activity.

The development of cochlear implants involved solving numerous bioengineering challenges, and improvements are still ongoing. Drs. Clarke, Hochmair, and Wilson have contributed at multiple points and in diverse ways to the development of this technology. Dr. Clarke is a surgeon and an auditory physiologist. Beginning in the 1960s, he built a multidisciplinary team to develop the cochlear implant. Dr. Clarke's team implanted its first multi-channel prototype in the late 1970s and received FDA approval for the procedure in 1985. I will mention a charming story that illustrates the creative mind at work. While at the beach one day, Dr. Clarke was playing with turban shells — the spiral shells that look like a cochlea — and he realized that if one wants to thread a fine twig as far as possible into the shell's interior, then the twig needs to be of gradually varying stiffness, with the part of the twig that is being threaded into the tightest spiral being the most flexible. He then applied this insight to design a wire bundle of varying stiffness for the cochlear implant so that when the surgeon threads it into the cochlea, it does minimal damage to the surrounding tissues. Dr. Hochmair is an electrical engineer. In collaboration with her husband Dr. Erwin Hochmair, she began working on cochlear implant technology in the 1970s. The Hochmairs developed a multi-channel prototype in the late 1970s and later founded the MED-EL Corporation to further develop and commercialize the cochlear implant. Dr. Ingeborg Hochmair has served as CEO and chief technology officer of MED-EL since its founding, and under Dr. Hochmair's leadership, MED-EL has solved many of the bioengineering challenges in cochlear implant design and manufacturing. Dr. Wilson is also an electrical engineer. Beginning in the 1980s and working at the Research Triangle Institute in North Carolina, he developed signal processing algorithms — most famously the method of continuous interleaved sampling — which have greatly improved the performance of cochlear implants, especially in the context of speech recognition. I note that Dr. Wilson's work was funded by the NIH with the idea that his algorithms would be made freely available — thus allowing the cochlear implant manufacturers to incorporate his algorithms into their devices with no delays or constraints.

Drs. Clark, Hochmair, and Wilson, on behalf of the Lasker Foundation and the many millions of hearing impaired individuals worldwide, we salute you for your seminal contributions to the development of the cochlear implant.

Graeme M. Clark

Acceptance remarks, 2013 Lasker Awards Ceremony

I feel very honored to be a co-recipient of the prestigious Lasker~DeBakey Award in Clinical Medical Research, especially as it recognizes research that has led to the multi-channel cochlear implant or bionic ear — the first clinically successful interface between the world and human consciousness. It is also the first advance in helping severely-to-profoundly deaf children communicate since Sign Language of the Deaf began 250 years ago.

My passion to help deaf people started as a teenager when I experienced what it was like for my deaf father as a pharmacist in country Australia — he said years later of his deafness "it has been an enormous handicap, it affects your whole life, there is nothing so embarrassing as not being able to hear people properly." But in 1967, when I started my research journey there was much skepticism — it had been said "direct stimulation of the auditory nerve fibres with resultant perception of speech is not feasible."

Nevertheless, I commenced an uncertain journey by leaving a senior surgical position to do research in auditory brain science. And when I discovered in 1970 that multi-channel electrical stimulation would be needed there was nowhere to go to further the research. Fortunately, the University of Melbourne appointed me to establish the first ENT and audiology departments in Australia, but I still had few staff and little money. I pay tribute to the young graduates who shared the vision, stood on the streets of Melbourne shaking a tin and asking for money, and turned the ENT Department into an engineering one.

When all was ready, I interviewed my first experimental patient, Rod Saunders, in 1978. He said: "I would like to be able to hear something again. It's a nightmare being deaf. If it helps with speech I will be very grateful." It has also been a means of learning about brain function and what underlies human consciousness. I can now say after a tumultuous ride personally, that Rod and many thousands like him can now have their life back again. This has been in no small measure due to an exciting partnership with Cochlear and their leadership in biomedical technology.

In conclusion, I would to thank the Lasker Foundation again for this honor, and I will endeavor to continue my search for excellence to help deaf people and others with neurosensory disorders such as blindness and paraplegia.

Ingeborg Hochmair

Acceptance remarks, 2013 Lasker Awards Ceremony

The cochlear implant is not a life-saving device. It is, however, very, very special, since it has to do with communication, with being able to take part in society. It is connected with every child's human right for education, and it can alleviate isolation and cognitive decline in older adults.

Clinical medical research is of particular importance in the field of CIs for at least three reasons:

Efficacy with CIs has to do with how well the sensory organ is replaced, it has to do with perception.

Secondly, since learning is involved with electrical stimulation, immediate and acute results of sound perception tests do not necessarily represent what the user will be able to perceive after getting used to the new input to their auditory system.

And thirdly, another very special aspect of cochlear implants is the enormous responsibility researchers and developers have to gently preserve the tiny delicate structures of the inner ear for future technologies. This is of special relevance with children born today with a life expectancy of maybe 120 years and with candidates who nowadays typically have hearing still present, that they hope and expect to be preserved.

It is very reassuring to follow the first pioneer patients, like C.K. from our series, who has been enjoying sound-only speech perception from a portable sound processor for 34 years by now. One cannot avoid to be passionate about clinical medical research in the field of CIs because of the close contact and trustful cooperation with users, which is not only essential but also fascinating.

The growth in research topics potentially resulting in further improved implant systems and the generation of evidence for new indications, is impressive.

What really needs to improve, is the global access to CIs: Just looking at deaf-born young children, 25,000 of them have received a CI last year, but five times as many would need to receive a CI and the necessary aftercare each year around the globe to enable them to learn to hear and speak, be properly educated, and become part of normal society.

I will be donating my portion of the award honorarium to Pink Crocodile, a seven-year-old charity organization led by experienced specialists providing education, tools, and financing for rehabilitation for Indian children with a hearing loss who have received either hearing aids or cochlear implants.

There is still so much to do in the field of CIs, and I am so much looking forward to the upcoming ever growing tasks!

Blake S. Wilson

Acceptance remarks, 2013 Lasker Awards Ceremony

Development of the modern cochlear implant was a worldwide effort involving many scientists, engineers, physician-scientists, and research subjects. The success of this effort is an outstanding example of the power of collaborations between the public and private sectors and also the informed support by the NIH of applied as well as basic research.

I am proud to stand before you today as a representative of the worldwide effort, and I am especially proud to stand with Graeme Clark and Ingeborg Hochmair, who are two of my heroes and the foremost living pioneers in our field.

Although the present cochlear implants are truly wonderful, room still exists for improvements. A variability in outcomes remains, and even the top-performing patients experience difficulties in understanding speech in adverse acoustic environments such as noisy restaurants or workplaces. In addition, reception of sounds more complex than speech — such as music — is less than satisfying for most patients. Research is underway to narrow or even eliminate these gaps between prosthetic and fully functional hearing, and to narrow the range of outcomes such that all patients will achieve high levels of performance. Many promising possibilities are being pursued by extraordinarily talented investigators, and I am completely confident that further improvements will be made.

An even more important challenge — in my mind — is to make the highly effective technology we have today available to all persons who could benefit from it. Thus far, about 320 thousand persons have received a cochlear implant in one or both ears. But various estimates indicate that as many as 25 million persons worldwide could benefit from a cochlear implant. That means that only about 1 or 2 percent of the population who could benefit actually have received a cochlear implant.

The cochlear implant is a transformative technology that allows children to be mainstreamed into regular schools, adults to have a wide range of job opportunities, and all recipients to connect in new and important ways with their families, friends, and society at large. The resulting human and economic benefits are immense.

In many parts of the world, cost is a barrier to widespread applications of the technology, even though the benefits ultimately far outweigh the cost. The principal expenses are in providing the appropriate medical infrastructure and care. The cost of the device also plays a role, but that cost is coming down and is not the dominant factor for most countries. Several of us in this room are working to reduce or remove the cost barrier, and to improve hearing health care worldwide, which includes prevention, screening, and treatments in addition to cochlear implants.

This magnificent award will greatly increase awareness of how cochlear implants can enable severely and profoundly deaf persons to realize their full potential in life, and that awareness will in turn facilitate further dissemination and development of this marvelous technology. Thank you for welcoming Graeme, Ingeborg, and me into the Lasker family, and thank you for the highly favorable tailwind you have given us and our colleagues to do more!